NEUROGENIN1 and NEUROGENIN2 control two distinct waves of neurogenesis in developing dorsal root ganglia

Abstract

Different classes of sensory neurons in dorsal root ganglia (DRG) are generated in two waves: large-diameter trkC + and trkB + neurons are born first, followed by small-diameter trkA + neurons. All such neurons require either neurogenin (ngn) 1 or 2, two neuronal determination genes encoding basic helix-loop-helix (bHLH) transcription factors. ngn2 is required primarily if not exclusively for the generation of trkC + and trkB + neurons, whereas the generation of most or all trkA + neurons requires ngn1. Comparison with previous lineage tracing data in the chick suggests that this dichotomy reflects a requirement for the two ngns in distinct sensory precursor populations. The neurogenesis defect in ngn2 −/− embryos is transient and later compensated by ngn1-dependent precursors, suggesting that feedback or competitive interactions between these precursors may control the proportion of different neuronal subtypes they normally produce. These data reveal remarkable parallels in the roles of bHLH factors during neurogenesis in the DRG, and myogenesis in the neighboring myotome.

Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development

“…Similarly, neurons differentiate upon expression of Ngn1, 2, or 3 (Sommer et al, 1996;Ma et al, 1999;Hand et al, 2005;Ge et al, 2006). In the cortex, Ngn2 also promotes the migration of neurons through long distances to reach their final position and form the typical layered organization (Hand et al, 2005;Ge et al, 2006).…”

Geminin's Double Life: Chromatin Connections that Regulate Transcription at the Transition from Proliferation to Differentiation

“…These are expressed in proliferating neuronal precursors and are critical for neuronal cell fate determination, as evidenced in Ngn1 and Ngn2 mutant mice, which show deficits of cranial and spinal sensory ganglia and ventral spinal cord neurons. [6][7][8][9] Conversely, NeuroD is expressed in committed, post-mitotic neurons and is required for neuronal differentiation (reviewed in refs. 10 and 11).…”

Visualization of bHLH transcription factor interactions in living mammalian cell nuclei and developing chicken neural tube by FRET

“…Consistent with these expression patterns, the Mash1/E47 and Ngn2/E47 pair showed higher FRET efficiencies in their expression regions of neural tube, suggesting that they might form the functional protein-DNA complexes with their target genes in the medial and lateral part, respectively. The complementary expression pattern for Mash1 and Ngn2 has been found in many locations of mouse developing nervous system and proved to be functionally relevant in these regions, as the ventral telencephalon progenitor and autonomic neurons for Mash1, and the dorsal telencephalon progenitor and sensory neurons for Ngn2 [40,42,45,46]. Based on these observations, we propose that the complementary activities of Mash1 and Ngn2 during nervous system development might be conserved in vertebrates.…”

“…Targeted disruption of Mash1 in mice resulted in neurogenesis defects in multiple regions of the nervous system, including the ventral telencephalon and olfactory sensory epithelium [42][43][44]. Ngn1 or Ngn2 single knockout mice showed complementary loss of cranial sensory ganglia, whereas the Ngn1/2 double knockout mice lacked the spinal sensory ganglia as well as a majority of ventral spinal cord neurons, due to, as for Mash1, an early defect in neurogenesis [40,45,46]. NeuroD1 null mice have defects in the granule layers of the cerebellum and hippocampus, and in the inner ear sensory neurons because of a later function of NeuroD1 in neuronal differentiation [47,48].…”