ui Zheng

Developmental basis of sexually dimorphic digit ratios.

Males and females generally have different finger proportions. In males, digit 2 is shorter than digit 4, but in females digit 2 is the same length or longer than digit 4. The second- to fourth-digit (2D:4D) ratio correlates with numerous sexually dimorphic behavioral and physiological conditions. Although correlational studies suggest that digit ratios reflect prenatal exposure to androgen, the developmental mechanism underlying sexually dimorphic digit development remains unknown. Here we report that the 2D:4D ratio in mice is controlled by the balance of androgen to estrogen signaling during a narrow window of digit development. Androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas inactivation of ER-α increases growth of digit 4, which leads to a lower 2D:4D ratio. We also show that addition of androgen has the same effect as inactivation of ER and that addition of estrogen mimics the reduction of AR. Androgen and estrogen differentially regulate the network of genes that controls chondrocyte proliferation, leading to differential growth of digit 4 in males and females. These studies identify previously undescribed molecular dimorphisms between male and female limb buds and provide experimental evidence that the digit ratio is a lifelong signature of prenatal hormonal exposure. Our results also suggest that the 2D:4D ratio can serve as an indicator of disrupted endocrine signaling during early development, which may aid in the identification of fetal origins of adult diseases.

SIAMESE, a Plant-Specific Cell Cycle Regulator, Controls Endoreplication Onset in Arabidopsis thaliana

Recessive mutations in the SIAMESE (SIM) gene of Arabidopsis thaliana result in multicellular trichomes harboring individual nuclei with a low ploidy level, a phenotype strikingly different from that of wild-type trichomes, which are single cells with a nuclear DNA content of ∼16C to 32C. These observations suggested that SIM is required to suppress mitosis as part of the switch to endoreplication in trichomes. Here, we demonstrate that SIM encodes a nuclear-localized 14-kD protein containing a cyclin binding motif and a motif found in ICK/KRP (for Interactors of Cdc2 kinase/Kip-related protein) cell cycle inhibitor proteins. Accordingly, SIM was found to associate with D-type cyclins and CDKA;1. Homologs of SIM were detected in other dicots and in monocots but not in mammals or fungi. SIM proteins are expressed throughout the shoot apical meristem, in leaf primordia, and in the elongation zone of the root and are localized to the nucleus. Plants overexpressing SIM are slow-growing and have narrow leaves and enlarged epidermal cells with an increased DNA content resulting from additional endocycles. We hypothesize that SIM encodes a plant-specific CDK inhibitor with a key function in the mitosis-to-endoreplication transition.

Functional diversification of MYB23 and GL1 genes in trichome morphogenesis and initiation

The functional diversification of duplicated genes is one of the driving forces in evolution. To understand the molecular mechanisms of gene diversification, we studied the functional relationship of the two Arabidopsis paralogous MYB-related genes GL1 and MYB23. We show that MYB23 controls trichome branching and trichome initiation at leaf edges. The latter is controlled redundantly together with GL1. We show that the two proteins are functionally equivalent during trichome initiation but not during trichome branching. RT-PCR and reporter construct analysis revealed spatial, temporal and genetic differences in transcriptional regulation of the GL1 and MYB23 genes. Presented data indicate that the diversification of GL1 and MYB23 gene functions occurred at the level of cis-regulatory sequences with respect to trichome initiation, and that, in parallel, the diversification with respect to regulation of trichome branching also involved changes in respective proteins.

The PRETTY FEW SEEDS2 gene encodes an Arabidopsis homeodomain protein that regulates ovule development

The PRETTY FEW SEEDS2 gene encodes a homeodomain protein that regulates ovule development. In peptide alignments spanning the homeodomain and the WOX domain, PFS2 shared 95% amino acid identity with the PRESSED FLOWER and WUSCHEL proteins. In the pfs2-1 allele, the integuments display morphological abnormalities and 95% of the embryo sacs fail to develop properly, which results in reduced fecundity. PFS2 transcripts were most abundant in developing ovules, which accounts for the ovule phenotype in pfs2 mutants. In addition, PFS2 transcripts were present in developing primordia and differentiating organs, but, interestingly, they were absent during cell maturation. Ectopic PFS2 expression interfered with differentiation of primordia from meristems. For most plants, this resulted in fasciated stems, altered phyllotaxy, a cessation of primordia differentiation, or a combination of these. In the plants that made ovules, ectopic PFS2 expression blocked megaspore mother cell differentiation and often impeded polarized growth of the outer integument. PFS2 activity altered AGAMOUS expression, which accounts for some of the gain- and loss-of-function phenotypes. Based on analyses presented here, PFS2 affects either ovule patterning or differentiation.

Sonic hedgehog controls growth of external genitalia by regulating cell cycle kinetics

The faithful positioning and growth of cells during embryonic development is essential. In this study Seifert et al. demonstrate that inactivation of Sonic Hedgehog during development of the genital tubercle results in a prolonged G1 phase and a slower rate of growth.

Genetic Footprints of Stamen Ancestors Guide Perianth Evolution in Persea (Lauraceae)

The perianth of Persea americana (Lauraceae) consists of two whorls of morphologically similar laminar organs, termed tepals. Closely related Persea borbonia, however, produces a dimorphic perianth with smaller outer tepals. To assess whether homologues of floral organ identity genes in Persea may play a role in shaping this dimorphic perianth, we compared their expression patterns in the two species. A homologue of AP1 (A‐function) is expressed at low levels in both perianth types but was not tepal specific. Homologues of AGL6, however, show the tepal‐specific expression pattern expected of A‐function genes. Homologues of AP3 and PI (B‐function) are expressed in tepals of both perianth types, indicating that perianth dimorphism in Persea is not regulated by these genes. Differential expression across the dimorphic perianth as absence late in outer tepal development was evident for homologues of AG (C‐function) and SEP3 (E‐function). Genetic studies in model systems indicate a conserved role for AG homologues in specifying stamen and carpel identity, but the expression pattern in Persea indicates a novel role in perianth development. On the basis of gene expression and the occasional presence of tepaloid organs in stamen whorls, we hypothesize that the tepals of Persea and perhaps other Lauraceae are derived from stamens.

Mediator subunit18 controls flowering time and floral organ identity in Arabidopsis.

Mediator is a conserved multi-protein complex that plays an important role in regulating transcription by mediating interactions between transcriptional activator proteins and RNA polymerase II. Much evidence exists that Mediator plays a constitutive role in the transcription of all genes transcribed by RNA polymerase II. However, evidence is mounting that specific Mediator subunits may control the developmental regulation of specific subsets of RNA polymerase II-dependent genes. Although the Mediator complex has been extensively studied in yeast and mammals, only a few reports on Mediator function in flowering time control of plants, little is known about Mediator function in floral organ identity. Here we show that in Arabidopsis thaliana, MEDIATOR SUBUNIT 18 (MED18) affects flowering time and floral organ formation through FLOWERING LOCUS C (FLC) and AGAMOUS (AG). A MED18 loss-of-function mutant showed a remarkable syndrome of later flowering and altered floral organ number. We show that FLC and AG mRNA levels and AG expression patterns are altered in the mutant. Our results support parallels between the regulation of FLC and AG and demonstrate a developmental role for Mediator in plants.

Development and evolution of the unique cetacean dentition.

The evolutionary success of mammals is rooted in their high metabolic rate. A high metabolic rate is sustainable thanks to efficient food processing and that in turn is facilitated by precise occlusion of the teeth and the acquisition of rhythmic mastication. These major evolutionary innovations characterize most members of the Class Mammalia. Cetaceans are one of the few groups of mammals in which precise occlusion has been secondarily lost. Most toothed whales have an increased number of simple crowned teeth that are similar along the tooth row. Evolution toward these specializations began immediately after the time cetaceans transitioned from terrestrial-to-marine environments. The fossil record documents the critical aspects of occlusal evolution of cetaceans, and allows us to pinpoint the evolutionary timing of the macroevolutionary events leading to their unusual dental morphology among mammals. The developmental controls of tooth differentiation and tooth number have been studied in a few mammalian clades, but nothing is known about how these controls differ between cetaceans and mammals that retain functional occlusion. Here we show that pigs, a cetacean relative with regionalized tooth morphology and complex tooth crowns, retain the typical mammalian gene expression patterns that control early tooth differentiation, expressing Bmp4 in the rostral (mesial, anterior) domain of the jaw, and Fgf8 caudally (distal, posterior). By contrast, dolphins have lost these regional differences in dental morphology and the Bmp4 domain is extended into the caudal region of the developing jaw. We hypothesize that the functional constraints underlying mammalian occlusion have been released in cetaceans, facilitating changes in the genetic control of early dental development. Such major developmental changes drive morphological evolution and are correlated with major shifts in diet and food processing during cetacean evolution.

Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies

Significance Birth defects of external genitalia occur at a striking frequency, affecting ∼1:250 live births. Congenital penile anomalies (CPAs) encompass a range of malformations, including failure of urethral tube closure (hypospadias), penile curvature (chordee), micropenis, and feminization of male genitalia. Both genetic anomalies and exposures to endocrine disrupting chemicals (EDCs) are suspected to be involved; however, little is known about the underlying causes or the developmental window(s) of sensitivity to antiandrogenic or estrogenic signals. This study shows that disruption of androgen signaling at different stages of genital development can induce different types of CPA. We identify a cell type in which the androgen receptor (AR) is essential for genital masculinization and uncover previously unknown mechanisms through which antiandrogenic and estrogenic signals induce penile malformations. Congenital penile anomalies (CPAs) are among the most common human birth defects. Reports of CPAs, which include hypospadias, chordee, micropenis, and ambiguous genitalia, have risen sharply in recent decades, but the causes of these malformations are rarely identified. Both genetic anomalies and environmental factors, such as antiandrogenic and estrogenic endocrine disrupting chemicals (EDCs), are suspected to cause CPAs; however, little is known about the temporal window(s) of sensitivity to EDCs, or the tissue-specific roles and downstream targets of the androgen receptor (AR) in external genitalia. Here, we show that the full spectrum of CPAs can be produced by disrupting AR at different developmental stages and in specific cell types in the mouse genital tubercle. Inactivation of AR during a narrow window of prenatal development results in hypospadias and chordee, whereas earlier disruptions cause ambiguous genitalia and later disruptions cause micropenis. The neonatal phase of penile development is controlled by the balance of AR to estrogen receptor α (ERα) activity; either inhibition of androgen or augmentation of estrogen signaling can induce micropenis. AR and ERα have opposite effects on cell division, apoptosis, and regulation of Hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling in the genital tubercle. We identify Indian hedgehog (Ihh) as a novel downstream target of AR in external genitalia and show that conditional deletion of Ihh inhibits penile masculinization. These studies reveal previously unidentified cellular and molecular mechanisms by which antiandrogenic and estrogenic signals induce penile malformations and demonstrate that the timing of endocrine disruption can determine the type of CPA.

FLORAL DEVELOPMENTAL MORPHOLOGY OF PERSEA AMERICANA (AVOCADO, LAURACEAE): THE ODDITIES OF MALE ORGAN IDENTITY

A floral developmental series was determined for Persea americana (Lauraceae, avocado), and the floral morphology of this species was compared with available data for other members of Persea. We compared the structure of the inflorescence and flower with that of vegetative shoots with respect to phyllotaxy and leaf shape. The inflorescence is a determinate thyrse (panicle) with variable numbers of lateral branches. Staminal glands in Persea may represent abaxial‐marginal emergences rather than stamens. However, these glands are occasionally involved in transitions to pollen sacs and ovary margins. Stigmas, pollen sacs, staminal appendages, glands of staminodes, and margins of tepals share features that are subjectively associated with “androecia.” In the innermost androecial whorl, staminodial glands appear united because of the reduction of the middle portion to a staminodial apex. The apex of staminodes is homologous to the filament and anther, as well as to the stigma of the carpel, and corresponds to the connective tip in other basal angiosperms. In Persea, the connective and the staminode apex also correspond to the body of the tepal (i.e., all but the margin). Above a constriction (stipe), the carpel forms a cross zone bearing the single ovule; this cross zone also corresponds to the thecae in stamens, similar to observations for other basal angiosperms.