Regulation of sympathetic and enteric nervous system development by Hand2

Abstract

The sympathetic nervous system (SNS) and enteric nervous system (ENS) employ many of the same signaling pathways and transcription circuits to regulate their development. However, while the SNS is a relatively simple nervous system, with neurons predominantly noradrenergic, the ENS is composed of neurons that are as diverse as those found in the central nervous system. This suggests that molecules regulating development of these two nervous systems function in both unique and in overlapping roles. The Hand2 basic helix‐loop‐helix transcription factor is expressed in both the SNS and ENS during development and our analysis of Hand2 function in mice shows that it regulates similar and unique events during their development. In the SNS, Hand2 is required for proliferation, survival and noradrenergic differentiation of neurons. Analysis of the transcriptional circuit regulating catecholaminergic differentiation showed that it does not affect expression of GATA3. Phox2a or Phox2b suggesting that it may directly regulate genes encoding the norepinephrine biosynthetic enzymes. In the ENS, loss of Hand2 leads to changes in the ratios of neurons expressing different neuronal transmitters and in ENS patterning. We will present a comparative analysis of how Hand2 regulates different aspects of SNS and ENS development.