Krox-20 gene expression: Influencing hindbrain-craniofacial developmental interactions

Abstract

Krox-20 is a C(2)H(2)-type zinc-finger transcription factor that plays an essential role in hindbrain development. The Krox-20 null mutation results in hindbrain anomalies that result in neonatal death due to respiratory and feeding deficits. Here we review our studies of how the Krox- 20 null mutation impacts the development of motor and sensory systems critical for the production of consummatory behaviors (suckling/chewing). First, we demonstrated that Krox-20 null mutants suffer a selective loss of primary jaw-opening muscles during prenatal development. In vivo and in vitro studies are reviewed that highlight intrinsic defects in mutant jaw-opener muscles that contribute to muscle degeneration. Next we focus on the impact of the mutation on proprioceptive neurons activated during consummatory behaviors. Mesencephalic trigeminal (Me5) neurons are primary sensory neurons that relay jaw proprioception to the central nervous system. These cells are unique because their cell bodies are located in the central as opposed to the peripheral nervous system. Data are reviewed that demonstrate the impact of the mutation on Me5 neurons, a cell group traditionally thought to emerge from the mesencephalon. We show that Krox-20 null mutants have twice as many Me5 neurons relative to wildtypes at E15, but by birth have half the number of Me5 cells as wildtypes. TUNEL assays performed in each set of studies reveal that Krox-20 expression acts to protect both muscle and mesencephalic trigeminal neurons against apoptosis, suggesting that Krox-20, in addition to its role in hindbrain patterning, has a broader, long-lasting role in development.

Human endometrial stromal cell decidualization requires transcriptional reprogramming by PLZF†

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Early growth response 2 regulates mouse cooperative behavior

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Egr2 induction in Drd1+ ensembles of the ventrolateral striatum supports the development of cocaine reward

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