ME1 and GE1: Basic Helix – Loop – Helix Transcription Factors Expressed at High Levels in the Developing Nervous System and in Morphogenetically Active Regions

Abstract

Several class A basic helix-loop-helix (bHLH) transcription factors have been cloned from the developing mouse and chick nervous system. The cloned cDNAs (ME1, ME2, ME3, ME4, in the mouse and GE1, GE2 in the chick) have HLH coding regions highly homologous to other known class A bHLH genes. The genes corresponding to ME1 and GE1 are abundantly expressed during development of the central nervous system. ME1 and GE1 are expressed in proliferating neuroblasts and in cells at the initial stages of differentiation (for example in the external granule cell layer of the cerebellum and in the lateral region of the ventricular zone in the developing neural tube and cortex). They are also expressed at high levels in morphogenetically active regions such as limb buds, somites and mesonephric tubules. The expression of ME1 and GE1 decreases once cellular differentiation is over. Based on the expression of ME1 and GE1 in regions of active cellular proliferation and differentiation and on the known role of other bHLH factors in development, we suggest that ME1 and GE1 play important roles during development of the nervous system as well as in other organ systems.

Helix‐loop‐helix transcription factors regulate Id2 gene promoter activity

“…Expression of several class A bHLH transcription factors and Id-like transcriptional regulators is downregulated during differentiation [9,24,25,30,31] and stimulated when cells are induced to proliferate [32,33]. Also, overexpression of Id2 potentiates proliferation which is likely related to its ability to bind Rb protein [34].…”

“…In developing nervous system, class A bHLH transcription factors [9,25] and Id2 [24] are expressed in the ventricular zone where proliferating cells are localized. Expression of El2 and MEI become downregulated in developing neurons when they migrate from the ventricular zone.…”

“…All the CAT constructs were sequenced using primer in the CAT gene. Full length cDNAs for bHLH transcription factors MEla, ME2, Id2 [9,10,24], and NSCL1 [13] were cloned into eukaryotic expression vector pRcCMV (Invitrogen). Double stranded mutated E-box cluster A and B oligonucleotides were cloned into the blunted XbaI site of the pBLCAT2 [26] reporter plasmid in the front of herpes simplex virus thymidine kinase promoter.…”

“…The medium was changed to normal growth media 12 to 18 h after transfection. Cells were harvested 48 h later and CAT assays were performed as described [9,24]. Quantiration of acetylation ratios was obtained by PhosphorImager analysis (Molecular Dynamics).…”

“…E-mail: toomas@lamar.colostate.edu neuronal populations are born, the expression of Id2 is down regulated in neuroepithelial cells and continues to be high in early borned neurons. Class A bHLH transcription factors MEI [9] and El2 [25] are expressed in proliferating neuroblasts and their expression is downregulated after cells migrate out from the ventricular zone and initiate differentiation. ME2 (ITF2), a member of class A bHLH family, is expressed in both proliferating neuroblasts and differentiating neurons in several regions of the developing nervous system [10].…”