The basic helix-loop-helix factor Hand 2 regulates autonomic nervous system development.
Mammalian autonomic nervous system (ANS) development requires the combinatorial action of a number of transcription factors, which include Mash 1, Phox 2b, and GATA 3. Here we show that the bHLH transcription factor, Hand 2 (dHAND), is expressed concurrently with Mash 1 during sympathetic nervous system (SNS) development and that the expression of Hand 2 is not dependent on Mash 1. This suggests that these two bHLH factors work in parallel during SNS development. We also show that ectopic expression of Hand 2 activates the neuronal program and promotes the acquisition of a phenotype corresponding to peripheral neurons including neurons of the SNS lineage in P19 embryonic carcinoma cells. We propose that Hand 2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mash 1. We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand 2 functions to promote ANS development as part of a larger transcriptional complex.
Morikawa
Yuka
Y
Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA.
Dai
Yan-Shan
YS
Hao
Jianming
J
Bonin
Christopher
C
Hwang
Sunny
S
Cserjesi
Peter
P
D000818:Animals; D001341:Autonomic Nervous System / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D018345:Mice, Knockout; D014158:Transcription, Genetic / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D050880:p300-CBP Transcription Factors; C499317:Ascl1 protein, mouse; C498766:Hand2 protein, mouse