The neural connections that endow humans with great dexterity are also present in mice at birth, but are suppressed shortly afterward, a new study reveals. A key feature distinguishing the corticospinal (CS) system of higher primates from other species is hand dexterity control. This dexterity likely arises from particular connections between CS neurons and motor neurons that control hand muscles in higher primates. In other mammals, these connections may fail to develop, or they may form and then become actively eliminated. Here, Zirong Gu and colleagues identify the mechanism that suppresses development of connections between CS neurons and motor neurons in mice shortly after birth. In mice just a few days old, they identified an area in the corticospinal tract (CST), in which connections to motor neurons form, yet which was undergoing synaptic pruning, a process where neural connections are lost. By selectively deleting receptors, the researchers found one in particular, PlexA1, that when deleted or inhibited caused mice to retain their CST-motor neural connections, and perform better in dexterity tests. In early human development, expression of PLEXA1 is weak in the layer of the brain responsible for CST-motor neural connections, the authors note, but not in mice during the equivalent period of postnatal growth; yet when they induce human-like transcription within the CST, the mice experience similar neural growth in this layer. In speculating about the reasons behind the suppression of these connections, the authors suggest that perhaps increased manual dexterity offers no fitness advantages to four-legged animals, or perhaps it even imposes a fitness burden.