Generation of a Nkx2.2Cre knock-in mouse line: Analysis of cell lineages in the central nervous system

• Generation and validation of a mutant Nkx2.2Cre knock-in allele.
• Genetic labeling and tracing of Nkx2.2 descendants in the CNS.
• Monitoring the fate of progenitors in the absence of Nkx2.2.

A Nkx2.2cre knock-in mutant mouse line was generated that on the appropriate reporter strain enables cell fate analysis of the Nkx2.2 cell lineage in the central nervous system and elsewhere. We here demonstrate that Nkx2.2 lineage-marked cells reside in the ventral p3 region along the entire length of the CNS and also in pancreas of mouse embryos. Nkx2.2+ progenitor cells develop into V3 interneurons in spinal cord and generate the branchio-visceral motor nuclei of cranial nerves in hindbrain. Nkx2.2+ cells in hindbrain also form serotonergic neurons and oligodendrocytes during later developmental stages. In mouse mutants lacking Nkx2.2 protein the neuronal progenitor cells in spinal cord are transformed to the distinct fate of somatic motor neurons including their axonal projections that exit the CNS ventrally and no longer cross the midline at the commissure. These data identify Nkx2.2 as key regulator to determine neuronal subtypes in the p3 domain of the central nervous system.