From Neanderthal to Homo sapiens

Project background During the course of evolution, the human brain has undergone tremendous expansion. This has led to the development of complex neurocircuits of unmatched complexity, highly social behaviour, expanded language use and cognitive superiority. A small number of infants, however, are born with significantly smaller brains, a condition called primary microcephaly (PM). Infants with PM suffer from a number of symptoms including cognitive and motor impairments (i.e. babies are unable to sit before the age of 2 years), epilepsy, cerebral palsy, a delay in speaking and defects of the eyes, including retinal degeneration [1]. Some PM babies also show overall growth reduction, as is the case in Seckel or Meier-Gorlin Syndrome, which is then called microcephalic primordial dwarfism [2]. Such inborn cases of microcephaly are believed to result from defects in neural progenitor proliferation, differentiation or apoptosis during early development. Molecularly, microcephaly arises often from defects in centrosome biogenesis or DNA replication. Recently, we have shown that defects in ciliogenesis can similarly impact on brain development [3]. In order to identify new factors involved in brain expansion, Dr Travis Stracker (guest scientist of the graduate school in 2017) has mined the Neanderthal genome for genes, which have been adapted in the transition to the brain of homo sapiens. This collection of genes that show fixed changes in homo sapiens is rich with genes known to cause PM, suggesting that others may be candidates for neurodevelopmental disorders. In the proposed collaborative project we will investigate the molecular function of candidate genes on cell cycle progression, centrosomes and cilia in zebrafish and cell culture.