ABSTRACT
The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are coexpressed across multiple projection neuron subtypes. Here, we discover 17 CSMN-enriched microRNAs (miRNAs), 15 of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is a demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians' increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.
Subject(s)
Biological Evolution , Cerebral Cortex/physiology , Mammals/genetics , MicroRNAs/genetics , MicroRNAs/physiology , Animals , Corpus Callosum/physiology , Eutheria/genetics , Gene Expression Regulation, Developmental , Mice , Motor Cortex/pathology , Motor Neurons , Pyramidal Tracts/pathologyABSTRACT
The circulatory system consists of veins and arteries. Compared with arteries, veins have been neglected in cardiovascular research. Although veins are significantly less muscular than similarly sized arteries, the contribution of veins to cardiovascular homeostasis cannot be left un-noted because veins accommodate 70% of the circulating blood. Circulating blood platelets contain the majority of systemic 5-HT (5-hydroxytryptamine; serotonin). Similar to venous function, the physiological role of 5-HT in the cardiovascular system is not well understood. Here, we present not only a review on 5-HT and veins but ways in which these two topics might intersect in a physiologically relevant manner. Here we show the novel findings that veins exhibit higher amounts of intracellular 5-HT than arteries. Moreover, we also show evidence that, similar to arteries, veins have the ability to uptake 5-HT. In this review, we introduce the venous system as a reservoir for 5-HT in the periphery, suggesting that veins, in addition to arteries, may represent an important target for drugs that interfere with the serotonergic system. In addition, the serotonergic system from synthesis to metabolism, 5-HT receptor activation and venous diseases will also be discussed.
