Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus.

Molecular and Cellular Neurosciences
Jennifer M SkidmoreDonna M Martin

Abstract

Establishment of neuronal diversity is a central topic in developmental neurobiology. Prior studies implicated Pitx2, a paired-like homeodomain transcription factor, in mouse subthalamic nucleus neuronal development, but precise stages of neuronal differentiation affected (migration, axon outgrowth, fate specification) and underlying mechanisms were unknown. Here we report lineage tracing experiments using Pitx2(cre/+), Pitx2(cre/null), and conditional nuclear lacZ reporter mice to track embryonic Pitx2 expressing neurons. Migration of subthalamic nucleus and hypothalamic neurons was severely arrested in Pitx2(cre/null) embryos, and subclasses of subthalamic nucleus neurons identified by Lmx1b, Foxp1, and Foxp2-gene expression revealed differing sensitivities to Pitx2 dosage. Interestingly, embryonic subthalamic nucleus development was unaffected in Lmx1b null mice, suggesting that Pitx2 and Lmx1b act via independent genetic pathways. These data provide the first direct evidence for Pitx2-dependent neuronal migration in the developing hypothalamus, and demonstrate that complex transcriptional networks regulate regional specialization of distinct hypothalamic and subthalamic nucleus neurons.

Citations

Dec 18, 2013·Brain Structure & Function·Nicanor Morales-DelgadoCarmen Díaz
Nov 14, 2012·Molecular and Cellular Neurosciences·Mindy R WaiteDonna M Martin
Jan 20, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·M R WaiteD M Martin
Sep 8, 2011·Genesis : the Journal of Genetics and Development·Jennifer M SkidmoreDonna M Martin
Oct 15, 2013·The Journal of Comparative Neurology·Laura DomínguezNerea Moreno
Aug 16, 2014·Journal of Neuroscience Research·Mindy R Waite, Donna M Martin
Jan 30, 2015·Frontiers in Neuroanatomy·Carmen DíazLuis Puelles
Jun 30, 2010·Izvestiia Akademii nauk. Seriia biologicheskaia·P P AvdoninIu V Markitantova
Dec 10, 2016·Scientific Reports·Emanuel GasserMarkus Stoffel
Jun 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Marie BarbierPierre-Yves Risold
Nov 5, 2020·Brain Structure & Function·Raquel Murcia-RamónEduardo Puelles
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Lara López-GonzálezLuis Puelles

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