Ronghao Li

Activins, Inhibins, and Follistatins: Further Thoughts on a Growing Family of Regulators

Abstract Inhibin, a feedback inhibitor of pituitary FSH secretion, and its homodimer, activin, have been the subject of a growing body of literature in the last 5 years. These factors play a role not only in endocrine feedback in the reproductive system but also in paracrine and autocrine regulation of both reproductive and nonreproductive organs, including the liver, kidney, and brain. Additionally, the messages coding for both subunits and their receptors are exquisitely regulated, both spatially and temporally, during embryonic development. The cloning of a family of activin receptors; the development of specific immunoassays for inhibins A and B, and activins A and B; the description of α subunit, β subunit, and receptor loss of function transgenic mouse models; and the cloning of two new β subunit homologs have increased our understanding of the possible roles this complex family of proteins plays in development and endocrine function. This review largely confines itself to the roles of inhibins and activins in the male and female reproductive system, and is intended as an update to a 1992 review published in this journal.

Establishment of Schwann cell lines from normal adult and embryonic rat dorsal root ganglia

Schwann cells, an important component of the peripheral nervous system, interact with neurons to mutually support growth and replication in the embryo and survival and differentiated function in the adult. The ability of adult Schwann cells to re-enter the cell cycle after nerve injury is crucial to their role in nerve repair. This ability suggests that it should be possible to obtain non-transformed, cell lines which maintain the characteristics of proliferating adult Schwann cells in vivo, as well as obtaining Schwann cells from rapidly dividing embryonic tissues. One approach to obtaining normal functionally differentiated cell lines has been to start primary cultures in serum-free medium containing growth factors and attachment proteins specifically selected to favor the replication of the cell type of interest. By culturing dispersed dorsal root ganglia on laminin, in serum-free medium with hormones and growth factors, we repeatedly generate homogenous Schwann cell cultures which yield normal Schwann cell lines from the dorsal root ganglia (DRG) of both embryonic and adult rats. These cells maintain the phenotype of Schwann cells as determined by morphology and staining for GFAP, S100, p75 NGF receptor, laminin, and MAG production in co-culture with DRG neurons.

Multiple factors control the proliferation and differentiation of rat early embryonic (day 9) neuroepithelial cells

The proliferation and differentiation of neural precursor cells is largely controlled by environmental factors. By providing the factors that favor the proliferation or suppress the differentiation of this cell type, we isolated and expanded an early neuroepithelial pre-differentiated cell type from E9 rat neural plate in serum-free medium. This has led to the establishment of a neural epithelial precursor (NEP) cell line. The NEP cells properties are substantially different from those of cell lines previously derived from neural tissue at later stages of development. Initial selection and survival of this cell type requires a factor secreted by an embryonic Schwann (nrESC) cell line. Continued passage of these cells requires cell-cell contact for both survival and growth. Neural cell differentiation can be induced in this nestin positive precursor cell line by bFGF and forskolin. General neuronal markers, as well as cortical neuron-specific protein kinase C isozyme, and accumulation of glutamate and aspartate were induced in most cells. Choline acetyl-transferase was also induced in a small number of cells. When implanted into neonatal rat brain, the NEP cell line gave rise to several distinct neuronal and glial phenotypes in different regions of the brain including cerebellar cortex and hippocampus.

Culture of Pluripotent Neural Epithelial Progenitor Cells from E9 Rat Embryo

The mammalian central nervous system is developmentally derived from neuroepithelial cells in the neural plate. These neuroepithelial cells grow and differentiate in response to signals from their surrounding environment. Many of those signals have been well characterized and others remain to be discovered. In cell culture, a conditioned medium, a feeder cell layer, or a tissue extract has been used as supplement in addition to those factors well characterized for maintaining the multipotent status of neural progenitor cells. To date, there have been many types of neural progenitor cells established in culture from various stages of development and from different regions of the nervous system of various species. This chapter will provide a brief introduction to those cultures and a detailed method for culturing rat neural epithelial cells at embryonic stage E9 and characterizing them in vitro and in vivo.

Inhibin and Activin as Paracrine Regulators of Gonadal Function: In Vitro Model Systems

Inhibin and activin were first described as feedback inhibitors of pituitary function. However, a range of data now supports the hypothesis that these factors play a major role in the paracrine regulation of gonadal function (1, 2). Activin seems to act as a mitogen and morphogen during development. Both inhibin and activin, and their receptors and binding proteins, are also expressed during the normal cycling of the adult ovary (3) and testis. The exact response to these hormones, however, may vary with the developmental stage of the testis or ovary and the stage of the seminiferous or follicular cycle.