Oculomotor nerve guidance and terminal branching requires interactions with differentiating extraocular muscles

TWIST1, a gene associated with Saethre-Chotzen syndrome, regulates extraocular muscle organization in mouse

“…At E10.5, axons have exited the motor nuclei and begun growing towards the orbit. A few pioneer axons contact PITX2+ cells ventrolateral to the eye as early as E10.0 ( Bjorke et al, 2021 ). The majority of axons reach the orbit around E11.5, as the muscle anlage is differentiating ( Bjorke et al, 2021 ; Michalak et al, 2017 ).…”

“…A few pioneer axons contact PITX2+ cells ventrolateral to the eye as early as E10.0 ( Bjorke et al, 2021 ). The majority of axons reach the orbit around E11.5, as the muscle anlage is differentiating ( Bjorke et al, 2021 ; Michalak et al, 2017 ). Normally, CN3 travels ventrally from the oculomotor nucleus in the midbrain, through the region that will become the cavernous sinus, and enters the orbit.…”

“…Neither Twist1 nor Twist2-cre are expressed in motor neurons, so these neuronal changes must be secondary to the muscle changes. In the complete absence of EOMs, motor neurons target the orbit correctly, but then fail to make correct terminal branches and many later die ( Bjorke et al, 2021 ; Michalak et al, 2017 ). The exact branching errors depend on the genetic strategy used to ablate the EOMs.…”

Impaired Extraocular Muscle Innervation Is Present Before Eye Opening in a Mouse Model of Infantile Nystagmus Syndrome

“…OMNs in the brainstem are born between E9.5 and E11.5 and extend axons toward the orbit beginning at E10.0, with branches to each EOM established by E13.5. 18 – 22 From heterozygous matings, we generated E13.5 litters with wild-type and albino embryos that express GFP in the motor neurons ( Isl MN : GFP ) and prepared whole mounts. CN3, CN4, and CN6 axonal trajectories developed normally onto EOMs in albinos and in controls ( Figs.…”

“… 50 EOMs also influence axon guidance during early development. 19 , 22 , 51 How motor neuron subtypes are matched with the proper myofiber subtype is not fully understood, although there is evidence in skeletal muscles of a retrograde influence of myofiber subtype on motor neuron specification. 44 An imbalance in the proportion of slow and fast motor neurons or abnormalities in NMJ development of one type of OMN could underlie the differences in proportions of myofiber subtypes seen in albinos.…”