Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation

TLDR

Motor neuron differentiation is accompanied by the expression of the LIM homeodomain transcription factor Islet1 (ISL1). The study aims to determine whether ISL1 is necessary for motor neuron generation. The authors examined neural tube cell differentiation in embryos lacking ISL1 via gene targeting. ISL1 is essential for motor neuron production, and its absence also blocks differentiation of EN1+ interneurons, which can be rescued by motor neuron‑containing regions, indicating that motor neuron generation is a prerequisite for certain interneuron differentiation.

Abstract

Motor neuron differentiation is accompanied by the expression of a LIM homeodomain transcription factor, Islet1 (ISL1). To assess the involvement of ISL1 in the generation of motor neurons, we analyzed cell differentiation in the neural tube of embryos in which ISL1 expression has been eliminated by gene targeting. Motor neurons are not generated without ISL1, although many other aspects of cell differentiation in the neural tube occur normally. A population of interneurons that express Engrailed1 (EN1), however, also fails to differentiate in Isl1 mutant embryos. The differentiation of EN1+ interneurons can be induced in both wild-type and mutant neural tissue by regions of the neural tube that contain motor neurons. These results show that ISL1 is required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons.