Lmo4 synergizes with Fezf2 to promote direct in vivo reprogramming of upper layer cortical neurons and cortical glia towards deep-layer neuron identities
Fig 8
Model of Fezf2/Lmo4 synergistic reprogramming effect on pyramidal neurons (A) and glial cells (B). (A) By electroporating (IUE) Fezf2 and Lmo4 in UL neurons normally projecting contralaterally either at embryonic E14.5 or postnatally, these neurons acquire a DL-like signature and tend to project outside of the cortex to subcerebral targets, such as the striatum, thalamus, IC, CP, and/or SC. This lineage conversion is more efficient in the motor (M1) than in the somatosensory (S1) cortex and at prenatal than at postnatal stages. (B) Injection of a retrovirus either carrying Neurog2/Bcl2 (NB), Neurog2/Bcl2 and Fezf2 (NBF), or Neurog2/Bcl2 and Fezf2/Lmo4 (NBFL) into P5 cortical proliferative glial cells leads to increased complexity and a higher proportion of iNs to express the DL marker Ctip2. CP, cerebral peduncle; DL, deep layers; IC, internal capsule; IUE, in utero electroporation; SC, spinal cord; UL, upper layers.