Interaction of MTG family proteins with NEUROG2 and ASCL1 in the developing nervous system.

During neural development, members of MTG family of transcriptional repressors are induced by proneural basic helix-loop-helix (bHLH) transcription factors and in turn inhibit the activity of the bHLH proteins, forming a negative feedback loop that regulates the normal progression of neurogenesis. Three MTG genes, MTG8, MTG16 and MTGR1, are expressed in distinct patterns in the developing nervous system. Various bHLH proteins are also expressed in distinct patterns.

Progenitor cell maturation in the developing vertebrate retina.

Progenitor cells in the developing retina initially divide so that each division produces two cells that divide again. Subsequently, progenitor cells change their mode of division so that one or both cells produced by a division can withdraw from the mitotic cycle and differentiate. We asked how these two progenitor cell stages differ molecularly and what controls the switch in the mode of division.

Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis.

The sequential steps of neurogenesis are characterized by highly choreographed changes in transcription factor activity. In contrast to the well-studied mechanisms of transcription factor activation during neurogenesis, much less is understood regarding how such activity is terminated. We previously showed that MTGR1, a member of the MTG family of transcriptional repressors, is strongly induced by a proneural basic helix-loop-helix transcription factor, NEUROG2 in developing nervous system.

Regulation of ganglion cell production by Notch signaling during retinal development.

Although progenitor cells in developing vertebrate retina are capable of producing all retinal cell types, they are competent to produce only certain cell types at a given time, and this competence changes as development progresses. We asked whether a change in progenitor cell competence is primarily responsible for ending production of a specific cell type, the retinal ganglion cell. Reducing Notch expression using an antisense oligonucleotide in vitro or in vivo increased ganglion cell genesis.

Plane of cell cleavage and numb distribution during cell division relative to cell differentiation in the developing retina.

Progenitor cells in the early developing nervous system can divide symmetrically, giving rise to two daughter cells that divide again, or asymmetrically, giving rise to one cell that differentiates and one that divides again. It has been suggested that the orientation of the cell cleavage plane during mitosis determines the type of division. A marker of early cell differentiation, the RA4 antigen, was used to identify regions of the developing chick retina with and without differentiating cells, and the orientation of the cleavage plane was characterized for mitotic figures in each region.