A LIM-homeodomain combinatorial code for motor-neuron pathway selection

Abstract

Different classes of vertebrate motor neuron that innervate distinct muscle targets express unique combinations of LIM-homeodomain transcription factors, suggesting that a combinatorial code of LIM-homeodomain proteins may underlie the control of motor-neuron pathway selection. Studies of LIM-homeodomain genes in mouse, Drosophila melanogaster and Caenorhabditis elegans have revealed functions of these genes in neuronal survival, axon guidance, neurotransmitter expression and neuronal function, but, to our knowledge, none of these studies have addressed the issue of a functional code. Here we study two members of this gene family in Drosophila, namely lim3, the homologue of the vertebrate Lhx3 and Lhx4 genes, and islet, the homologue of the vertebrate Isl1 and Is12 genes. We show that Drosophila lim3 is expressed by a specific subset of islet-expressing motor neurons and that mutating or misexpressing lim3 switches motor-neuron projections predictably. Our results provide evidence that lim3 and islet constitute a combinatorial code that generates distinct motor-neuron identities.

A Novel Missense Mutation (P366T) of the LHX4 Gene Causes Severe Combined Pituitary Hormone Deficiency with Pituitary Hypoplasia, Ectopic Posterior Lobe and a Poorly Developed Sella Turcica

“…Our mutation (P366T) was located in the C-terminus of LHX4. The exact functional of the C-terminus of LHX3 and LHX4 has been unknown; however, the 35-amino acid region at the C-terminus of LHX3 and LHX4 is well conserved and shows no significant similarity to other proteins [12,16,20]. This fact suggests that this region may have some specific role in LHX3 and LHX4.…”

“…LHX3/Lhx3 and LHX4/Lhx4 are the LIM homeodomain protein family and are characterized by two LIM domains and a homeodomain [12,14,16]. In general LIM homeodomain genes are widely expressed throughout development in complex and often overlapping patterns, implicating these genes in a variety of regulatory events [12,14,16].…”

“…In general LIM homeodomain genes are widely expressed throughout development in complex and often overlapping patterns, implicating these genes in a variety of regulatory events [12,14,16]. Lhx4 of mouse is expressed in the developing neural tube, hindbrain, Rathke's pouch, and pituitary gland [16][17][18]. Disruption of the mouse Lhx4 gene has demonstrated the defect of proliferation of all anterior pituitary cell lineages and abnormal differentiation of corticotroph, resulting in anterior pituitary hypoplasia [17,18].…”

“…In general LIM homeodomain genes are widely expressed throughout development in complex and often overlapping patterns, implicating these genes in a variety of regulatory events [12,14,16]. Lhx4 of mouse is expressed in the developing neural tube, hindbrain, Rathke's pouch, and pituitary gland [16][17][18].…”

A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4

“…They have one tandem pair of LIM domains and one homeodomain, and are also transcriptional factors for neurogenesis (Sharma et al, 1998;Sheng et al, 1997;Thor et al, 1999). The LIM domain is a cysteine-rich sequence recognized in the three homeobox gene products, Lin-1, Iyl-1, and Mec-3 (Dawid et al, 1998;Dawid and Chitnis, 2001;Freyd et al, 1990).…”