Anita Schuchardt

BMPs as Mediators of Roof Plate Repulsion of Commissural Neurons

During spinal cord development, commissural (C) neurons, located near the dorsal midline, send axons ventrally and across the floor plate (FP). The trajectory of these axons toward the FP is guided in part by netrins. The mechanisms that guide the early phase of C axon extension, however, have not been resolved. We show that the roof plate (RP) expresses a diffusible activity that repels C axons and orients their growth within the dorsal spinal cord. Bone morphogenetic proteins (BMPs) appear to act as RP-derived chemorepellents that guide the early trajectory of the axons of C neurons in the developing spinal cord: BMP7 mimics the RP repellent activity for C axons in vitro, can act directly to collapse C growth cones, and appears to serve an essential function in RP repulsion of C axons.

RET proto-oncogene is important for the development of respiratory CO2 sensitivity

Brain stem muscarinic cholinergic pathways are important in respiratory carbon dioxide (CO2) chemosensitivity. Defects in the muscarinic system have been reported in children with congenital/developmental disorders of respiratory control such as sudden infant death syndrome (SIDS) and congenital central hypoventilation syndrome (CCHS). This early onset of disease suggests a possible genetic basis. The muscarinic system is part of the autonomic nervous system which develops from the neural crest. Ret proto-oncogene is important for this development. Thus, a potential role for ret in the development of respiratory CO2 chemosensitivity was considered. Using plethysmography, we assessed the ventilatory response to inhaled CO2 in the unanesthetized offsprings of ret +/- mice. Fractional increases in minute ventilation during hypercapnia relative to isocapnia were 5.1 +/- 3.2, 3.0 +/- 1.6 and 1.4 +/- 0.8 for the ret +/+, ret +/- and ret +/- mice, respectively. The ret knockout mice have a depressed ventilatory response to inhaled CO2. Therefore, the ret gene is an important factor in the pathway of neuronal development which allow respiratory CO2 chemosensitivity.

AXON GUIDANCE : A COMPELLING CASE FOR REPELLING GROWTH CONES

The guidance of axons to their targets represents a key stage in the assembly of the nervous system, linking the early inductive interactions that establish neuronal identity to the later steps of synapse formation. Neurons are required to extend axons through a variety of cellular environments, and the task of perceiving, integrating, and responding to the myriad signals present in the immediate vicinity of the axon falls to the growth cone, a sensory and motor apparatus located at the distal tip of the developing axon. Attempts to unravel the mechanisms of axonal guidance have centered on four main issues: the cellular strategies used to influence the rate of extension and the orientation of growth cones; the nature of molecules in the local environment of the axon that control growth cone behavior; the identity of receptors on the surface of growth cones that respond to these guidance cues; and the intracellular machinery that integrates multiple extracellular signals to produce the coordinated and directed response of growth cone navigation. The first wave of information on the cellular and molecular mechanisms of growth cone navigation emphasized positive influences on growth cone behavior through the identification of cell, axon, and substrate adhesion molecules that enhance the rate of axon extension and of chemoattractants that entice growth cones to distant targets. It took longer to appreciate that growth cone navigation also depends on negative influences, despite several early cellular assays that showed that contact with a variety of cell types inhibits growth cone motility (Walter et al., 1990; Goodman and Shatz, 1993; Schwab et al., 1993; Keynes and Cook, 1995). The first indications of the nature of proteins that cause growth cone inhibition have emerged over the past 2 years, and several papers in the current issues of Cell and Neuron now advance significantly the case that the guidance of axons, in both vertebrates and invertebrates, is dependent on proteins that inhibit or repel growth cones. These papers focus on two families of proteins, the semaphorinslcollapsins and the netrins. Intriguingly, the netrins have previously been implicated in the attraction of axons, suggesting that distinctions in the nature of guidance cues reside more in the response properties of growth cones than in the identity of environmental signals. Cellular Origins of Growth Cone inhibition In the 198Os, assays of growth cone behavior and axon navigation in vitro began to suggest the existence of signals that guide axons by repelling growth cones (Kapfhammer and Raper, 1987; Walter et al., 1987; Schwab et al., 1993; Keynes and Cooke, 1995). Of critical importance for the identification of relevant molecules was the develMinireview

RET‐deficient mice: an animal model for Hirschsprung's disease and renal agenesis

Abstract. Receptor tyrosine kinases play a critical role in transducing signals involved in cell growth and differentiation. The c‐ret proto‐oncogene is a member of the receptor tyrosine kinase gene superfamily originally identified by its transforming ability. Somatic mutations of c‐ret are responsible for a large proportion of thyroid papillary carcinomas, while germ‐line mutations are responsible for multiple endocrine neoplasia types 2A and 2B, dominantly inherited cancer syndromes characterized by multiple tumours of neuroectodermal origin. In addition to its role in tumour formation, c‐ret is thought to have a developmental role since mutations of the gene have been implicated in the aetiology of Hirschsprungs syndrome (congenital megacolon). A targeted mutation in the murine c‐ret locus shows that the ret receptor is required for normal development of two lineally unrelated systems, the excretory system and the enteric nervous system.

How Do Secondary Level Biology Teachers Make Sense of Using Mathematics in Design-Based Lessons About a Biological Process?

In the fall of 2011 five secondary level biology teachers in the northeast United States implemented an experimental instructional module that challenged their students with a design problem. This challenge required students to perform both mathematical analysis and the engineering application of biological concepts in order to reach a resolution. Specifically, given the parental genotypes of two gecko parents, students were tasked to: (a) mathematically represent the relative frequency of all possible offspring genotypes; and (b) design a systematic breeding program for the geckos that would consistently produce a rare and highly desired genotype as a result. Presented here is a study of how the participating teachers made sense of the mathematics and engineering design applied to the biological process of inheritance, and their reflections on their own implementations of the instructional module. Emergent themes dealt with the limitations of mathematics in teachers’ own biology education, their lack of experience with either engineering or design, and their efforts to help students address similar circumstances.