Regulation of neurogenesis by interactions between HEN1 and neuronal LMO proteins

Basic-helix-loop-helix transcription factors regulate neurogenesis and neur onal differentiation by as Set unknown mechanisms. We show that an embryoni c neuronal-specific basic-helix-loop-helix protein, HEN1 (also known as NSC L1 or NHLH), interacts with 'LIM only' proteins. Examination of the express ion patterns of XHEN1 and XLMO-3, the Xenopus homologues of these human gen es, reveals extensive overlap during early neurogenesis: at the onset of ga strulation on the dorsal side of the blastopore lip and, subsequently, in t he prospective neural plate. Binding of XLMO-3 increases the transcriptiona l activity of XHEN1 in vivo. Co-expression of these two genes in Xenopus em bryos induces a cascade of expression of neuronal-specific basic-helix-loop -helix proteins that leads to neuronal differentiation. We propose that XHE N1, in concert with XLMO-3, is a critical regulator of neurogenesis.