Disease relevance of Tlx3

• Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure [1].
• Rnx deficiency results in congenital central hypoventilation [1].

High impact information on Tlx3

• Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice [1].
• In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata [1].
• Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1 [2].
• Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive from Mash1-positive neural precursors, and depend on two related homeobox genes, Rnx and Tlx-1, for proper formation [2].
• In addition, as in Phox2b-deficient mice, the development of most (nor)adrenergic centers is compromised in Rnx mutants [3].
• Ectopic expression of Tlx3 in mouse embryonic stem cells is sufficient to enhance the development of glutamatergic neurons upon in vitro neuronal differentiation [4]

Biological context of Tlx3

• Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord [5].
• Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes [6].

Anatomical context of Tlx3

• Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3 [3].
• The difference in the spatio-temporal pattern between Tlx3-/- and Pbx3-/- suggests different levels of functional disorder of the respiratory center [7].
• During the early phase of neurogenesis, Gsh1/2 and Ascl1 coordinately regulate the expression of Tlx3, which is a critical postmitotic determinant for dorsal glutamatergic sensory interneurons [8].
• We report that the differentiation and migration of the superficial dorsal horn neurons are regulated by the LIM homeobox gene Lmx1b, and its downstream targets Rnx and Drg11, two transcription factors implicated in the development of dorsal horn circuitry [9].
• Onset of Tlx-3 expression in the chick cerebellar cortex correlates with the morphological development of fissures and delineates a posterior transverse boundary [10].

Associations of Tlx3 with chemical compounds

• Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice [5].

Other interactions of Tlx3

• Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates [5].
• We also demonstrated optical images of the respiratory activity of two different lines of knock-out mice (Tlx3-/-, Pbx3-/-) that exhibit respiratory failure leading to neonatal death from dysfunction of central respiratory neuron activity [7].

References