Scientists reveal how the brain makes the same neuron type in different places
Researchers discovered that fruit fly neurons can develop into identical cell types through completely different genetic pathways, depending on where they form in the nervous system. The finding challenges conventional understanding of how genetic instructions work and could reshape how scientists approach neural engineering and disease treatment.
Originaltitel: Neuronal Cell Fate Specification by the Convergence of Different Spatiotemporal Cues on a Common Terminal Selector Cascade
Två olika genregulatoriska vägar kan aktivera samma cellödesbestämmande genkaskad och skapa identiska nervceltyper på olika anatomiska platser. Forskare från Linköpings universitet och Universidad Autónoma de Madrid identifierade hur neuropeptidneuroner av typen Nplp1 i fruktflugans nervsystem uppstår genom två skilda vägar. Thorax-ventrale Tv1-neuroner aktiveras via transkriptionsfaktorerna Antp, hth, exd, lbe och cas, medan dorsal-mediala dAp-neuroner styrs av Kr och pdm. Båda vägarna konvergerar på samma terminala väljarkaskad: colamp;gt;ap/eya→dimm→Nplp1. Denna konvergensmekanism förklarar hur identiska celltyper kan genereras från olika neuroblasten vid olika tidpunkter. För bolagsbyggare inom neurovetenskapen illustrerar resultatet att cellspecifikation är robust och modulär – en insikt som öppnar för mer flexibla in vitro-differentiationsprotokoll för neuronala celltyper och minskad känslighet för variationer i utgångsmaterial.
<p>Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: colamp;gt;ap/eyaamp;gt;dimmamp;gt;Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdmamp;gt;grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate.</p>