An emerging role for prdm family genes in dorsoventral patterning of the vertebrate nervous system.

Denise A Zannino,Charles G Sagerström

doi:10.1186/s13064-015-0052-8

Denise A Zannino, Charles G Sagerström

Open Access

https://doi.org/10.1186/s13064-015-0052-8

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Abstract

The embryonic vertebrate neural tube is divided along its dorsoventral (DV) axis into eleven molecularly discrete progenitor domains. Each of these domains gives rise to distinct neuronal cell types; the ventral-most six domains contribute to motor circuits, while the five dorsal domains contribute to sensory circuits. Following the initial neurogenesis step, these domains also generate glial cell types—either astrocytes or oligodendrocytes. This DV pattern is initiated by two morphogens—Sonic Hedgehog released from notochord and floor plate and Bone Morphogenetic Protein produced in the roof plate—that act in concentration gradients to induce expression of genes along the DV axis. Subsequently, these DV-restricted genes cooperate to define progenitor domains and to control neuronal cell fate specification and differentiation in each domain. Many genes involved in this process have been identified, but significant gaps remain in our understanding of the underlying genetic program. Here we review recent work identifying members of the Prdm gene family as novel regulators of DV patterning in the neural tube. Many Prdm proteins regulate transcription by controlling histone modifications (either via intrinsic histone methyltransferase activity, or by recruiting histone modifying enzymes). Prdm genes are expressed in spatially restricted domains along the DV axis of the neural tube and play important roles in the specification of progenitor domains, as well as in the subsequent differentiation of motor neurons and various types of interneurons. Strikingly, Prdm proteins appear to function by binding to, and modulating the activity of, other transcription factors (particularly bHLH proteins). The identity of key transcription factors in DV patterning of the neural tube has been elucidated previously (e.g. the nkx, bHLH and pax families), but it now appears that an additional family is also required and that it acts in a potentially novel manner.

Highlights

Function of the adult central nervous system (CNS) relies on neural circuits to control activity
Some genes involved in this process are known, but this review focuses on a new class of genes—the Prdm family—that appears to control gene expression during the formation of neurons along the embryonic DV axis
Emerging principles for Prdm function in the developing CNS Embryogenesis is replete with transcription factor “codes” and networks working in concert to specify and differentiate various cell types

Summary

Introduction

Function of the adult central nervous system (CNS) relies on neural circuits to control activity. The zinc finger motifs, as well as prolinerich domains and zinc knuckles, are likely to mediate binding of Prdm proteins to partner proteins to facilitate access to genomic sites Based on their association with DNA (directly or indirectly), as well as their ability to modify histones (directly or indirectly) and recruit transcriptional regulators, it is likely that Prdm family proteins function to regulate gene expression states. Multiple roles for Prdm proteins in dorsoventral patterning of the neural tube Shortly after neural tube closure, the neuroepithelium undergoes extensive transformations, including cell proliferation and specification, to give rise to various neuronal and glial cell types necessary for motor and sensory circuits This process requires several steps (Fig. 1): First, gene expression is initiated along the dorsoventral (DV) axis of the neural tube in response to morphogen gradients.

A Prdm Genes

Conclusions