Lab members:

	Troy Ghashghaei
	Christine Han
	Ralf Schmid
	Amelia Stanco
	Yukako Yokota

Anton Lab

CURRENT PROJECTS:

Molecular signals that regulate the establishment, development and differentiation of radial glial cells.

The aim of our project is to elucidate the signals that regulate the establishment, development and differentiation of radial glial cells. To examine the molecular signals regulating this process, we have focused on neuregulin growth factors (NRG) and their erbB receptors. We are using cell type-specific and inducible promoters to modulate the function of erbB receptors in a radial glial cell-specific, and developmental time specific fashion in cerebral cortex. They will provide a comprehensive view of the function of NRG-erbB signaling in radial glial development, in particular, and corticogenesis, in general.

Cytoskeletal dynamics and cell polarity during neuronal migration and corticogenesis

Molecular analysis of human neuronal migrational deficits strongly suggest that dynamic regulation of neuronal cytoskeleton leads to the sequential unfolding of the birth, migration, and placement of neurons in cortex. To explore the significance of cytoskeletal dynamics during neural development in cerebral cortex, we will identify and study regulators of the organization and activity of actin microfilaments or microtubules during distinct stages of neuronal migration in the developing cerebral cortex.

Furthermore, the function of radial glia during neuronal migration and corticogenesis depends on establishing and maintaining polarity. Thus we aim to define the molecular cues regulating the polarity of radial glia and analyze how the structural and molecular polarity of radial glia is translated into specialized functions (i.e., as a neural progenitor, migratory guide, or astrocyte precursor) of radial glia.

Specific cell-cell adhesion mechanisms that determine how neurons migrate to appropriate positions and coalesce into distinct layers in the developing cerebral cortex.

In order to elucidate the specific cell-cell adhesion related mechanisms that determine how neurons migrate and coalesce into distinct layers in the developing cerebral cortex, we have focused on the functions of SPARC- like 1 (SPARCL1) and a 3 integrin during cortical development. Our previous results indicate that a 3 integrin modulates neuron-radial glial interactions during neuronal migration and SPARCL1 is critical for the final placement of neurons in the developing cerebral cortex . We will use CNS specific a 3 integrin deficient mouse models and radial glia specific SPARCL1 transgenic mouse models to further explore the contributions of these molecules to the emergence of the cerebral cortex.

The role of neuregulins and their erbB receptors in the proliferation and migration of cells that form the rostral migratory stream.

Analysis of neuregulin function during early brain development has led to some insights into mechanisms at work during adult neurogenesis and migration. Neuregulins and their receptors, erbB2, erbB3 and erbB4 are all expressed in the adult rostral migratory stream (RMS) and subventricular zone (SVZ), a model system for adult neurogenesis. We are currently evaluating the hypothesis that the neuregulins and their erbB receptors play a role in the proliferation and migration of cells that form the rostral migratory stream, using various conditional erbB receptor null mice and cell type specific NRG transgenic mice.